Researchers find that acquisition of a new gene in gut bacteria gave way for first infecting the lungs before evolving into a deadly pathogen.
Yersinia pestis is a bacterium that is characterized by its ability to cause plague, an infectious disease that can be airborne or transmitted by flea bites and often fatal. Originally evolving from gut bacteria as a mild gastrointestinal infection, Y. pestis gained the ability to infect the lungs between 5,000 to 20,000 years ago—quick in evolutionary terms.
The ability of bacteria to adapt to new hosts and their environments within the body is a result of cumulative gains and losses of genetic elements throughout time as the species evolves. Currently, Y. pestis is causative in bubonic, septicemic, and pneumonic plagues in mammals, with the pneumonic plague being the deadliest form.
The pneumonic plague, caused by Y. pestis, has a fatally rate of almost 100% if left untreated. The disease begins as relatively asymptomatic but later results in severe inflammation and lesions of the lungs.
In order to identify when Y. pestis gained the ability to evolve from a gastrointestinal pathogen to one that causes the fatal pneumonic plague, researchers examined the ancestral strains of Y. pestis in mouse models.
Mice were infected with various strains of Y. pestis and their effects on mice survival and disease progression were monitored. Tissues of the mice were analyzed in order to establish a point in the bacteria’s evolution that would account for the characteristics associated with the pneumonic disease.
The researchers proposed that a specific plasmid—a circular DNA strand in a cell that replicates independently—is found in bacteria of the gastrointestinal tract. This plasmid encodes three proteins, where the Pla protein is of special interest. It is understood that the function of Pla is to catalyze reactions that convert the inactive precursor of an enzyme that destroys blood clots into its active form.
The Researchers inserted the Pla gene into a less lethal strain of Y. pestis into the lungs of healthy mice and its changes were observed accordingly. The team found that this new mutated strain acquired the ability to cause respiratory infection that is characteristic of the pneumonic plague; that is, the addition, adaptation, and expression of the Pla gene in Y. pestis was necessary in order for the observed changes to occur.
The Pla gene ultimately allows bacteria to escape from one area of the body to reach other parts through the bloodstream by destroying blood clots. The disease manifests itself as a severe lung infection in the form of pneumonia and has the potential to result in respiratory failure and death.
The findings from this study point to the conclusion that Y. pestis first evolved as a respiratory pathogen before evolving into other forms of plague, most notably the bubonic plague endemic—more commonly known as Black Death. Again, the researchers postulate that based on their data, subsequent insertions and modifications of the Pla gene gave way for rapidly evolving strains of disease from the Y. pestis bacteria over time. The conclusions made by the research team are revolutionary for their field.
Currently, antibiotics have been effective at fighting infection. However, there has been a widespread use of antibiotics and consequent emergence of superbugs. Given the study’s findings and the ability of bacteria to acquire new genes and evolve, it becomes important to understand the mechanism through which the changes occur, especially because small genetic changes in bacteria can have virulent effects.